Differential down-regulation of pulmonary β1- and β2-adrenoceptor messenger RNA with prolonged in vivo infusion of isoprenaline

Abstract

The down-regulation by isoprenaline of β1 and β2-adrenoceptors in rat lung was investigated at the receptor protein and messenger RNA level. Rats were treated with either isoprenaline or vehicle for 2 h, 1 day and 7 days. Isoprenaline treatment resulted in significant decreases of both β1- and β2-adrenoceptor density after 1 day with maximal decreases of 65 ± 7 and 65 ± 5% for β1- and β2-adrenoceptors, respectively, at 7 days. The administration of isoprenaline had no effect on binding affinities of either β1 or β2-adrenoceptors. β1-Adrenoceptor mRNA was significantly decreased by 58 ± 10, 73 ± 4 and 51 ± 11% at 2 h, 1 day and 7 days, respectively, after isoprenaline treatment. However, the β2-adrenoceptor mRNA was not changed at 2 h after treatment and was significantly decreased by 35 ± 11 and 45 ± 12% at 1 day and 7 days, respectively after treatment. This time course of β2-adrenoceptor mRNA correlated well with that of the transcription factor cyclic AMP response element binding protein-like DNA binding activity, determined by gel shift assay. These findings indicate the existence of distinct mechanisms for down-regulation of β1- and β2-adrenoceptors and suggest the involvement of cyclic AMP response element binding protein in the down-regulation of β2-arenoceptors in rat lung.